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Her-2/neu and Topoisomerase iiα in Breast Cancer

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Abstract

In breast cancer, the predominant genetic mechanism for oncogene activation is through an amplification of a gene. The HER-2 (also known as ErbB2/c-erbB2/HER-2/neu) oncogene is the most frequently amplified oncogene in breast cancer, and its overexpression is associated with poor clinical outcome. In addition to its important role in breast cancer growth and progression, HER-2 is also a target for a new form of chemotherapy. Breast cancer patients have been treated with considerable success since 1998 with trastuzumab, a recombinant antibody designed to block signaling through HER-2 receptor. HER-2 has also been implicated in altering the chemosensitivity of breast cancer cells to different forms of conventional cytotoxic chemotherapy, particularly of topoII-inhibitors (e.g., anthracyclines). Topoisomerase IIα gene is located just by the HER-2 oncogene at the chromosome 17q12–q21 and is amplified or deleted in almost 90% of the HER-2 amplified primary breast tumors. Recent data suggests that amplification and deletion of topoisomerase IIα may account for both relative chemosensitivity and resistance to anthracycline therapy, depending on the specific genetic defect at the topoIIα locus. Expanding our understanding of HER-2 amplification also changes its role in the pathogenesis of breast cancer. HER-2 is an oncogene that clearly can drive tumor induction and growth and is also a target for a new kind of chemotherapy, but its function as a marker for chemoselection may be due to associated genetic changes, of which topoisomerase IIα is a good example. Moreover, despite potential evidence that genes other than HER-2, such as topoisomerase IIα, may be more important predictors of therapeutic response in breast cancer, HER-2 status still has a very significant role in therapeutic selection, mainly as the major criterion for administering trastuzumab in treating breast cancer. Thus, the clinical and therapeutic importance of the HER-2 and topoisomerase IIα status to breast cancer management should only increase in the next few years.

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  1. Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland

    Tero A.H. Järvinen

  2. Genome Institute of Singapore, Singapore

    Edison T. Liu

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Järvinen, T.A., Liu, E.T. Her-2/neu and Topoisomerase iiα in Breast Cancer. Breast Cancer Res Treat 78, 299–311 (2003). https://doi.org/10.1023/A:1023077507295

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